What is the level of evidence for the amnestic effects of sedatives in pediatric patients? A systematic review and meta-analyses

BACKGROUND Studies have suggested that benzodiazepines are amnestic drug par excellence, but when taken together, what level of evidence do they generate? Are other sedatives as amnestic as benzodiazepines? The aim of this study was to assess the level of scientific evidence for the amnestic effect of sedatives in pediatric patients who undergo health procedures. METHODS The literature was searched to identify randomized controlled trials that evaluated anterograde and retrograde amnesia in 1-19-year-olds who received sedative drugs during health procedures. Electronic databases, including PubMed, Scopus and Cochrane Library besides clinical trial registries and grey literature were searched. Two independent reviewers performed data extraction and risk of bias assessment using the Cochrane Collaboration's Tool. The meta-analyses were performed by calculating relative risk (RR) to 95% confidence intervals (CI). The quality of the evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS Fifty-four studies were included (4,168 participants). A higher occurrence of anterograde amnesia was observed when benzodiazepines, the most well-studied sedatives (n = 47), were used than when placebo was used (n = 12) (RR = 3.10; 95% CI: 2.30-4.19, P<0.001; I2 = 14%), with a moderate level of evidence. Higher doses of alpha2-adrenergic agonists (clonidine/dexmedetomidine) produced more anterograde amnesia than lower doses (n = 2) (RR = 1.83; 95% CI: 1.03-3.25; P = 0.038; I2 = 0%), with a low level of evidence; benzodiazepines' amnestic effects were not dose-dependent (n = 3) (RR = 1.54; 95% CI: 0.96-2.49; P = 0.07; I2 = 12%) but the evidence was low. A qualitative analysis showed that retrograde amnesia did not occur in 8 out of 10 studies. CONCLUSIONS In children, moderate evidence support that benzodiazepines induce anterograde amnesia, whereas the evidence for other sedatives is weak and based on isolated and small studies. Further clinical trials focused on the amnesia associated with non-benzodiazepine sedatives are therefore needed. TRIAL REGISTRATION PROSPERO CRD42015017559.